title: Osteogenic effect of local, long versus short term BMP-2 delivery from a novel SPU-PLGA-βTCP concentric system in a critical size defect in rats.
abstract: A concentric delivery system, composed of the three biomaterials SPU, PLGA, and βTCP (segmented polyurethane, poly[lactic-co-glycolic acid], and β-tricalcium phosphate) was fabricated as an external, porous ring of βTCP with a pasty core of a new SPU, mixed with PLGA microspheres. The regenerative effects of two distinct doses of either immediately available or continuously released rhBMP-2 were evaluated in an 8mm, critical calvaria defect in rats. Protein dose and release kinetics affected material resorption rates and the progression of the regeneration process. Groups treated with the empty system alone or in conjunction with free rhBMP-2 did not respond. By contrast, after 12 weeks, approximately 20% and 60% of the defects implanted with systems loaded with 1.6 μg and 6.5 μg rhBMP-2, respectively were healed, with all the growth factor being released in the course of 6 weeks. The NMR, FTIR, GPC, DSC, and histological analyses showed that PLGA microsphere degradation occurred independently of the regenerative process. However, the resorption rate of the SPU and βTCP did depend on the regeneration process, which was governed by dose and release rate of rhBMP-2. Furthermore, the biocompatibility and high capacity of adaptation to the defect convert the herein proposed, new SPU polymer into a potential material for applications in tissue engineering and regenerative medicine.
authors.affiliation: Department of Chemical Engineering and Pharmaceutical Technology, University of La Laguna, 38200 La Laguna, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Évora
authors.forename: A
authors.initials: A
authors.lastname: Delgado
authors.forename: R
authors.initials: R
authors.lastname: Reyes
authors.forename: A
authors.initials: A
authors.lastname: Hernández-Daranas
authors.forename: I
authors.initials: I
authors.lastname: Soriano
authors.forename: J
authors.initials: J
authors.lastname: San Román
authors.forename: C
authors.initials: C
authors.lastname: Evora
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000737:chemistry*; D016503:Drug Delivery Systems; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011140:Polyurethanes / Q000737:chemistry*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D012886:Skull / Q000293:injuries
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011140:Polyurethanes; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate; C115016:polyetherurethane; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: BMP-2; Bone regeneration; In vivo degradation; SPU–PLGA–βTCP system; Sustained delivery